Cirp protects against tumor necrosis factor-α-induced apoptosis via activation of extracellular signal-regulated kinase

Toshiharu Sakurai, Katsuhiko Itoh, Hiroaki Higashitsuji, Kohsuke Nonoguchi, Yu Liu, Hirohiko Watanabe, Tadasu Nakano, Manabu Fukumoto, Tsutomu Chiba, Jun Fujita

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we analyzed the effects of low culture temperature (32 °C) and cold-inducible RNA-binding protein (Cirp) expression on apoptosis in vitro. In BALB/3T3 cells treated with tumor necrosis factor (TNF)-α and cycloheximide, the down-shift in temperature from 37 °C to 32 °C increased the expression of Cirp and suppressed the apoptosis. Activation of caspase-8 was suppressed, and the level of phosphorylated extracellular signal-regulated kinase (ERK) was increased. Transduction of Cirp into the Cirp-deficient mouse fibroblasts increased the level of phosphorylated ERK and suppressed the TNF-α-induced apoptosis both at 37 °C and 32 °C. The ERK-specific inhibitor PD98059 decreased the cytoprotective effect of Cirp as well as that of low culture temperature. These data suggest that mild hypothermia protects cells from TNF-α-induced apoptosis, at least partly, via induction of Cirp, and that Cirp protects cells by activating the ERK pathway.

Original languageEnglish
Pages (from-to)290-295
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1763
Issue number3
DOIs
Publication statusPublished - 2006 Mar

Keywords

  • Apoptosis
  • Cirp
  • ERK
  • Hypothermia
  • TNF-α

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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